In order to test therapeutics for Alzheimer's disease (“AD”), it can be important to first be able to assess disease progression. Underlying clinical progression in AD can include neuropathologic changes that follow a pattern of spreading atrophy throughout the brain, starting in the medial temporal lobe. (See, e.g., Reference 1). With the prospect of disease-modifying therapies, early detection and accurate monitoring of such progression can be an important goal. The most frequently studied in vivo marker for AD progression is the brain atrophy rate derived from serial magnetic resonance imaging (“MRI”). Numerous cross-sectional studies have reported the average brain volume loss in AD to be several times greater than approximately 0.5%/year rate in non-demented elderly. (See, e.g., References 2-5). Accelerated within-subject brain volume loss has also been reported. (See, e.g., Reference 6).
Serial imaging facilitates specific assessment of progression, as the patient serves as his or her own reference baseline. In addition to AD, assessments of brain atrophy rates can also be of importance in hydrocephalus, traumatic injury and multiple sclerosis, since they can help gauge brain insult and its response to treatment. (See, e.g., References 7-9).
As early as in the 1980s, serial CT imaging studies showed abnormally large ventricular and sulcal enlargement in AD patients. Later, after the advent of MRI, the emphasis was placed on calculation of atrophy using MRI, given the better soft tissue Whereas there are virtually no published studies of brain atrophy in CT for Alzheimer's disease, modern CT has many advantages over MRI, including: (i) lower cost of both the imaging system and patient exam, (e.g., CT is less than about ½ of the cost of MRI), (ii) 100 times faster speed of acquisition (e.g., fewer motion artifacts), (iii) availability, (iv) spatial resolution, and (v) fewer limitations related to claustrophobia and the presence of ferromagnetic material (e.g., metal) in the body. The disadvantages of CT include lower contrast/noise, and exposure of the patient to ionized radiation. While radiation exposure can be of concern, the risk/benefit equation can be age- and organ-dependent, favoring the use of CT to study brain atrophy in the elderly.
Chronic subdural hematoma (“cSDH”) has become increasingly prevalent in the aging civilian and veteran population, and is projected to become the most common indication for an adult cranial procedure in the United States by 2030. (See, e.g., Reference 25). It is tenfold more common among Veterans Administration patients than civilians (see, e.g., Reference 25), and has a high mortality in the veteran population, with about 32% of afflicted patients between ages 65 and 96 dying within 1 year of diagnosis. (See, e.g., Reference 26). cSDH has a high recurrence rate (see, e.g., References 27, 28, 29, and 30), and patients often need prolonged hospitalization and rehabilitation. (See, e.g., References 31 and 32).
cSDH has traditionally been treated by surgical drainage via craniotomy or burr hole craniostomy in the operating room, or more recently, by twist drill craniostomy at the patient bedside. The purpose of drainage for cSDH is not only to relieve immediate mass effect on the brain, but also to remove toxic blood break-down products. Iron toxicity is a potential effector of cognitive outcome. (See, e.g., References 33, 34, 39, and 36). Increased extent of drainage of cSDH correlates with improved clinical outcomes, such as increased survival (see, e.g., Reference 37), reduced recurrence (see, e.g., References 38 and 39) and better functional outcome. (See, e.g., Reference 40).
Meta-analysis of 830 publications comparing craniotomy, burr holes and twist-drill for cSDH, found burr hole craniostomy to have the best outcome of the three treatment options by a narrow margin. After correction for selection bias, craniotomies resulted in the most deaths, burr holes resulted in the most nonfatal complications, and twist drills had the highest recurrence with the least proportion cured. (See, e.g., Reference 41). The increased recurrence of hematomas with twist drills has been found in several other studies (see, e.g., References 42, 43, 44 and 45) and it is hypothesized to be at least partially due to suboptimal drain placement. The current standard of care for twist drill craniostomy drainage of cSDH is that surgeon approximates optimal placement of the drain site with attention to the density, thickness and shape of the cSDH based on viewing of a series of two-dimensional CT More optimal placement of bedside twist drill craniostomies could potentially improve drainage, shorten hospitalization, reduce recurrence and improve cognitive outcomes. Since twist drills are performed at the bedside, with decreased anesthesia, their improved efficacy enable decreased perioperative anesthetic complications.
Thus, it may be beneficial to provide an exemplary system, method and computer-accessible medium for the determination of accelerated brain atrophy, radiodensity and optimal drainage site using CT, which can overcome at least some of the problems presented herein above.